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The NextOrganoid project: Developing animal-free brain organoids to encourage uptake and help uncover more breakthroughs in Parkinson’s disease

Professor Jens Schwamborn, University of Luxembourg - Animal Free Research UK

Professor Jens Schwamborn

Professor Jens Schwamborn

OrganoTherapeutics

Professor Jens Schwamborn is undertaking a pilot study to develop animal-free 3D brain organoids to study Parkinson’s disease. He aims to utilise them as an endorsement and exemplar to encourage and motivate other Parkinson’s and brain researchers to adopt an animal-free approach, paving the way for more progress in tackling this condition.

 

Parkinson’s: a global disease on the rise

In the UK, one in 37 people will be diagnosed with Parkinson’s in their lifetime, that’s around 145,000 people suffering with this debilitating and progressive neurodegenerative condition. Ageing leads to a higher risk of developing the disease. Disability and death due to Parkinson’s disease, are increasing faster globally than any other neurological disorder, with over 8.5 million people affected.

Parkinson’s disease is caused by the loss of dopamine-producing nerve cells in part of the brain called the midbrain. Dopamine acts as a messenger between parts of the brain and nervous system that help control and co-ordinate body movements so if these nerve cells die or become damaged, tremors and slow and difficult movements can result.

Towards the development of an animal-free ‘mini-brain’ model to study Parkinson’s disease

Parkinson’s disease is a uniquely complex human disease – the causes and symptoms can’t be successfully mimicked in animals, and this has hitherto slowed down breakthroughs in finding new and effective treatments.

This is now more widely recognised and technologies that are based on growing human cells and tissues, such as 3D organoid (mini-organs) and organ-on-chip technology are gaining in popularity amongst the research community. However, current models still use animal-derived biomaterials, for example, to help human cells grow or to map cells and molecules within the models.

One example is ‘Matrigel’ (derived from mice) which helps cells to attach, move and grow. Antibodies from animals are also commonly used as ‘markers’ to flag molecules within the organoids so they can be located and identified with specialised microscopes. Antibodies are traditionally made by animals when they are injected with a foreign substance that kicks starts their immune system to fight it. The animal is then repeatedly bled until sufficient amounts of the antibody are produced. Over 1 million animals in Europe alone are suffering through this procedure.

As well as being inhumane, one of the major scientific flaws in using animal-derived biomaterials is that there are differences between subsequent ‘batches’ of the material (known as ‘batch- to batch variation’) and this can lead to unreliable experimental results.

Professor Schwamborn is replacing animal antibodies with lab-synthesised human antibodies which are made using genetic engineering to instruct bacteria for example, to produce unlimited amounts of the same human antibody. As well as being more humane, repeat batches are identical, meaning more reliable experimental results and an unlimited supply of antibody, yielding greater efficiencies and cost effectiveness.

How will the animal-free mini brains be made?

Professor Schwamborn is creating a novel 3D brain organoid model that’s completely animal-free, which means using animal-free biomaterials (for example seaweed-derived growth media) to grow nerve cells and using human lab-made antibodies to study the brain organoids.

The human brain organoids themselves will be made from human induced pluripotent stem cells (iPSCs). These are cells derived from human skin or blood, which have had a ‘factory reset’, so can be reprogrammed back into an embryonic-like state. This enables the development of an unlimited source of any type of human cell needed, including nerve cells. Professor Schwamborn will specifically be replicating the midbrain, the site of nerve cell loss in Parkinson’s.

He is comparing the size of the organoids, their metabolic activity (i.e. the chemical reactions happening within them) and the dopamine produced with that of organoids made using animal-derived biomaterials. He’s also comparing the types of cells, their organisation and complexity. Professor Schwamborn is using human lab-made antibodies to identify the different brain cell types present (such as dopamine-producing nerve cells). He plans to show irrefutable evidence that animal-free 3D brain organoids are equally good, if not better than traditional brain organoids, made using animal-derived biomaterials.

The impact of this research

Professor Schwamborn will publish the results and freely share the protocols for creating these animal-free brain organoids to encourage their uptake in the wider scientific community and the model will provide a platform for uncovering insights about, and testing therapies for Parkinson’s disease. In addition to the 1 million animals suffering through antibody production in the European Union, this research could work towards replacing the 120,000 animals suffering for research into Parkinson’s disease in the EU.